Solid dispersion particles of tolbutamide (TBM) were prepared by formulating nonporous (Aerosil 200 (hydrophilic), Aerosil R972 (hydrophobic)) or porous (Sylysia 350 (hydrophilic), Sylophobic 200 (hydrophobic)) silica as a carrier and applying the spray-drying (SD) or evaporation (Eva) method. In the solid dispersion particles prepared by the SD method, TBM existed in a meta-stable form (Form II) irrespective of the type of silica. On the other hand, when the Eva method was used, various crystalline forms of TBM were observed in the solid dispersion particles according to the type of silica. Polymorphs of Forms III and IV were prepared with Aerosil 200 and Aerosil R972, respectively, while crystalline Form II was obtained when either of the forms of porous silica, Sylysia 350 or Sylophobic 200, was formulated. The dissolution property of TBM in the solid dispersion particles prepared with hydrophilic silica was remarkably improved compared with those of the original TBM crystals (Form I) or spray-dried TBM without silica (Form II). In the case of hydrophobic silica, the release rate of TBM from the solid dispersion particles was much slower than that of original TBM. The meta-stable form of TBM in the solid dispersion particles was stable for at least 4 weeks when stored at 60 degreesC and 0% RH, while the spray-dried TBM without silica (Form II) was gradually converted to the stable form (Form I) under the same storage conditions. Under the humid storage conditions (60 degreesC, 75% RH), the spray-dried TBM without silica (Form II) immediately converted into the stable form (Form I) within 1 day, while TBM (Form II) in the solid dispersions in a matrix of silica was stable for at least 1 week. (C) 2004 Elsevier B.V. All rights reserved.